WinNonlin® AutoPilot™ Getting Started Guide
Contents
1. is a configurable desktop application that works with Pharsight s industry leading PK PD analysis software WinNonlin and third party reporting tools including SigmaPlot and Microsoft Word and Excel to automate common or repetitive analyses AutoPilot can perform data transformations and PK and statistical analysis as well as create presenta tion quality tables graphs and text These formatted PK analysis outputs can then be directly inserted into documents such as presentations and reports for regulatory submissions WinNonlin AutoPilot can optionally interface with Pharsight s research management software Pharsight Knowledgebase Server for secure and trackable management of data analyses and output WinNonlin AutoPilot WinNonlin AutoPilot comprises two main functional modules the Adminis trator Module and the User Module You can use the Administrator Module to configure the formats nomenclature and data handling rules applied in the generation of PK analysis outputs to meet an organization s policies and stan dard operating procedures SOPs for analysis and reporting The User Mod ule consists of Automation and Comparison tools to automate PK analyses and compare output from automation runs You can use the User Module to specify selections for input study data analysis execution and output on a run by run basis Administrator and user selections are stored in XML Extensible Markup Language and PAP proprietary Phar2. Comments name name units precision restrictions Treatment_ Treatment No NA None A description of the Treatment a subject Description receives used both as sort variable in model and as output display Period Period No NA None The period of time that a Treatment was received Used primarily for statistical analy ses but also as both a sort variable and in output for Repeated Crossover designs Day Day No dec 0 Numeric Profile Day needed as a Sort model variable when more than one profile day in an auto mation run e g Day 7 and 14 Not needed for single dose Day 1 studies a In PKS mode an additional column called Treatment is also needed This column is a re quirement in mapping of data into PKS but 1s not used by AutoPilot Table 5 5 Demographic variables current defaults not mandatory WinNonlin Display name Default units Default Default restrictions Comments name precision Sequence Sequence NA NA Discrete alphanu Sequence of treatments meric received randomized cross over studies only Gender Gender NA NA Discrete values Subject sex male female Age Age year dec 0 Continuous numeric Subject age Race Race NA NA Discrete alpha e g Subject ethnicity Caucasian Wat Weight kg dec 1 Continuous numeric Subject body weight at screening Height Height cm dec 0 Continuous numeric Subject height BMI B
3. Microsoft Excel 2000 2003 20033 XP or XPJ XP or 2003 Microsoft NET Microsoft NET framework 1 1 NA For optional study data repository and reporting functions WinNonlin Enterprise edition with Pharsight Knowledgebase Server version 3 0 or later and PKS Reporter version 1 2 2 can be used in conjunction with AutoPilot Installing AutoPilot AutoPilot installation requires read write access to the Windows system direc tory and the installation directory The files in the Windows system directory are used internally by the application 14 Installation Installing AutoPilot 2 Also AutoPilot also requires write access to the folder C Program Files Pharsight AutoPilot APSystem as error logs are written to subfolders under that folder Note Installation on Windows 2000 or XP requires administrator rights AutoPilot installation To install AutoPilot 1 Confirm that the system meets the requirements outlined under System requirements on page 13 including required software 2 Close all Windows applications 3 If an anti virus program is running turn it off before installing AutoPilot Anti virus programs can severely degrade installation performance If the AutoPilot CD must be checked for viruses run the virus scanning software on the CD being sure to scan all compressed files before installing the applica tion 4 Insert the AutoPilot CD into the CD ROM drive If the Installation Wizard does not
4. User cannot modify these settings Introduction WinNonlin AutoPilot 1 Table 1 7 Formatted output all output Feature Configurable by administrator Configurable by user Variable and PK Admin can configure the display name to be User cannot modify these settings parameter nomenclature Used in the final output created by AutoPilot for mapping variables e g gender and PK parameters e g AUCinf Also Admin can configure the name of the PK parameter graph filenames PK parameter selection Admin can configure which PK parameters are User cannot modify which PK available to the user independent of specific parameters are available but can table but rather on model type including regi assign per table which PK parame men ters are displayed in the output Descriptive statistics Admin can configure which descriptive statistics User cannot modify which descrip selection are available to the user for the overall system tive statistics are available but can assign per table which PK parame ters are displayed in the output Precision selection Admin can configure the precisions per variable User can modify these precisions for the overall system per output and run Table 1 8 Formatted output graphs Feature Configurable by administrator Configurable by user Selection of Admin can determine which graphs are available and From the list of available graphs as gra
5. WinNonlin Under non PKS conditions all dosing information must be entered manually into WinNonlin before the model is saved for use in AutoPilot Lambda Z AutoPilot supports the following options all of which are set in the WinNon lin Lambda Z Ranges dialog Model gt Lambda Z Ranges in the WinNonlin menus 1 Disable curve stripping is selected no lambda z selections are assigned In this case WinNonlin does not calculate any PK Parameters that use the Lambda Z regression in their computation e g AUCinfinity Clearance Volume and subsequently no output is created with these parameters 2 Lambda Z ranges assigned by manual selection 3 No Lambda Z selections are made by default WinNonlin automatically assigns Lambda Z ranges per its algorithm see the WinNonlin User s Guide for details Partial AUCs Optionally you can assign partial AUC intervals manually in the NCA Model Model gt Partial Areas in the WinNonlin menus AutoPilot allows up to three partial AUC calculations per profile to be included in the output Model options The following selections are required for AutoPilot to function correctly Set these options in the WinNonlin Model Options dialog Model gt Model Options Study Preparation NCA model requirements 9 Output Options Select the following options only e Workbook e Chart e Exclude profiles with insufficient data Units Select units for the PK parameters These units are di
6. below 39 WinNonlin AutoPilot 4 Getting Started Guide Selg Graphs Time Concentration PK Parameter Categorical Standard Lambda_z Median Min and Max HL_Lambda_z Median E Min and Max Median Min and Max Mean 5D Mean 5B Mean 5D Mean SD Mean SD Mean SD Tmax Cmax AUClast AUCINF_obs Cl Fo bs Vz_F_obs Partial_Area w C w w w w w w w 17 Click the Tables tab The Tables window Selection tab is displayed In the left pane navigate to a table type such as Actual Times In the Selection tab pane click Remove All Note Some table types such as Lambda Z will have a Variables tab and a Statistics tab For table types with variables and statistics click Remove All for both 40 Testing the Installation Installation test PK Automation Demographics Actual Times Actual Times Deviation Concentration Cumulative AUC Lambda Z PK Parameter A PK Parameter B Intet PK Parameter Intext PK Parameter lt Remove All 18 Repeat step 17 for each remaining table category except Demographics to limit the number of tables produced for this sample run 19 Select Tables in the left pane and click the Table Types tab The Tables Type and Exclusion Criteria columns are displayed Select the appropriate Table options listed in Table Types window 41 WinNonlin AutoPilot 4 Getting Started Guide PK Automation el Sau Z Stratification Normalization
7. install the licenses is important First install the Win Nonlin license in the WinNonlin installation directory using the Pharsight License Wizard Then after you received by e mail the AutoPilot license information install the AutoPilot license in the AutoPilot installation direc tory using the AutoPilot License Install Wizard The license key code and product tracking ID 22 One license key code and one product tracking ID are included with each license or set of licenses purchased For mail shipments and computer down loads the key code and product tracking ID are sent by e mail For electronic Licensing Install an AutoPilot 1 1 1 license 3 license renewals the key code product tracking ID and license type are sent by e mail Include the product tracking ID in all correspondence with Pharsight Corpora tion about the product and its license including license renewals software updates and product upgrades Note Contact Pharsight Customer Support support pharsight com for sugges tions on automated deployment of network floating versions of Pharsight software Install an AutoPilot 1 1 1 license If you attempt to run AutoPilot 1 1 1 without first installing an appropriate license the following error message 1s displayed AutoPilot Message Encountered a WinNonlin AutoPilot license error Please check to make sure your WinNonlin AutoPilot license is okay To install a node license for AutoPilot 1 1
8. on a system for the first time to use Autopilot with PKS you must first load a study from PKS into WinNonlin To do this open WinNonlin select Load and select any study from PKS After performing this step you are able to load studies from PKS in Autopilot 3 SigmaPlot a In the spw ini file set the MaxNumberAutoLegends to at least 600 b In SigmaPlot go to Tools gt Options and click the Page tab Deselect the Graph objects resize with graph check box WinNonlin AutoPilot 2 Getting Started Guide 20 Chapter 3 Licensing Installation of AutoPilot software licenses AutoPilot requires installation of current license key codes for both AutoPilot and WinNonlin There are two types of license key codes l Anode license key code activates the software on the system on which it is installed The license agreement restricts installation of the software and license to a single personal computer PC per node license 2 A floating license key code enables multiple PCs in a networked environ ment to run the product using a shared pool of software licenses The number of simultaneous users is limited to the total number of licenses on the license server Installation Notes Install the license that applies to your application For the installation of the required WinNonlin licenses see additional directions in the WinNonlin Get ting Started Guide Node License An AutoPilot node license is sent via e mail The lic
9. 1 1 From the Windows Start menu go to All Programs gt Pharsight gt WinNonlin AutoPilot 1 1 1 gt AutoPilot License Install Wizard The Pharsight Licensing Wizard is displayed El Pharsight Licensing Wizard Please select the type of license purchased he product will work only on a specific PC e 3 fixed number of copies of the product can P malig Wears be used from any PC To address questions about licensing please contact Pharsight at litenset pharsight com or 419 052 4620 Close 2 Click Node License to install a node license for AutoPilot 1 1 1 23 WinNonlin AutoPilot 3 Getting Started Guide Figure 3 1 Install node license wizard Pharsight Licensing Wizard Install Node License Follow the steps below to install or update a Pharsight product node license key code 1 Type or paste in the Product Tracking ID included with your product shipment or license renewal e mail This number will be needed for all corespondence with Pharsight regarding this product license Product Tracking ID 2 Please enter the following user contact information optional User Name Department Company E mail Title Phone Tope or paste in the license key The license key was included with your product shipment or sent by Pharsight wia e mail License Keu Code o Click this button to install the license key Install License Key The information entered above will be saved to a file
10. 11 E a nena we eines 11 t RZ Oae T ET l s a AA A seeds 11 Licensing and product upgrades o 12 Customer teca roads nace 12 INSTallatiON sia A a i n 13 System regure Ss atari Macca eta der SAGs RR isa 13 Installine Auto Hilo iS Ana Powe E AI eee 14 ZIGOR a a TA e ae is 15 Usage Tequitements sii a aaa 18 LICONSINO adri a ee ae oe eee 21 For WinNonlin version 5 0 1 2 0 0 eee eee nes 22 For WinNonlin versions 5 1 1 and higher oooooo o 22 The license key code and product tracking ID 22 Install an AutoPilot 1 1 1 license iia AA 23 Renewing a floating license key COde o ooooooooooooooooo ooo B AutoPilot floating license issue o ooo 2 WinNonlin AutoPilot Getting Started Guide Chapter 4 Testing the Installation oooooocorocornmno 29 AM AAA 29 Chapter 5 Study PrepalaltiOn sierras rica 45 Study dal paidir irer tirar iia tds 45 WarlaDle Mames reddere a ii nes 45 Data AT AO SS cares N eee Hgts eet suse dci Aun aa aes 46 Required data variables by study type ceca 49 NCA model requireiicnts 2 04 20 N asso ya gede es me ached ST TAR isa 51 Variable T n cedo ds adds 51 DOS TESTA id tia ii 54 PA NI R Bodh aE dint 54 Paral AWC Sida A ad el dE Es 54 AA bw been ti eek ee sleek es geese we ees 54 Chapter 1 Introduction WinNonlin AutoPilot paradigm data requirements and Pharsight Corporation contact information WinNonlin AutoPilot
11. Introduction WinNonlin AutoPilot 1 Table 1 4 Business rules tables continued Feature Display analyte matrix and day Configurable by administrator Admin can independently select as a default for the Matrix e g Plasma Analyte e g Parent and Day e g Day 1 to be dis played in the final table as headers Configurable by user User can independently select for the Matrix e g Plasma Analyte e g Parent and Day e g Day 1 to be displayed in the final table as headers Table 1 5 Formatted output tables Feature Selection of tables Configurable by administrator Admin can determine which tables are avail able for the user and from this list initially cre ate the default list of available tables Configurable by user From the list of available tables as set by Admin User can determine which of these tables are actually generated per run i e User can modify the default list set by Admin Selection of vari ables for tables For each table Admin can determine which variables are available for inclusion along with their order From the list of available vari ables Admin determines which variables are actually included and their default ordering in the generated table From the list of available table variables based on the Admin settings User can deter mine which of these variables are actually included in the table and their order per run i e Us
12. MI kg m2 dec 1 Continuous numeric Subject Body Mass Index LBW LBW kg dec 1 Continuous numeric Subject Lean Body Weight BSA BSA m2 dec 2 Continuous numeric Subject Body Surface Area Smoke Smoke NA NA Discrete values yes Subject smoking status no 48 Study Preparation Study data 9 Table 5 5 Demographic variables current defaults not mandatory WinNonlin name Default precision Display name Default units Default restrictions Comments Alcohol Alcohol NA NA Discrete values yes Subject status consumes 1 no alcohol or not Child_Pugh Child Pugh NA NA Discrete variable Subject Child Pugh classifi cation CrCL CrCL mL min sig 3 Continuous numeric Subject Baseline Creatinine Clearance Genotype Genotype NA NA Discrete alphanu Subject Baseline genotype meric e g status CYP2D6 Exten sive Required for randomized crossover study designs to conduct inferential sta tistics Required data variables by study type The following tables list which data variables are required or optional by study type and matrix plasma or urine Table 5 6 Variable requirements for plasma data NCA models 200 202 Variable Study Design RCT nRCT Replicated Parallel Trough All Subject Required Required Required Required Required Treatment_Description Required Required Required Required Required Period Required Optional Requ
13. Microsoft Internet Explorer 13 Microsoft Word version 14 Model NCA model requirements 51 Model options 54 N NCA dosing regimen 54 Lambda Z 54 model options 54 model requirements 51 partial AUCs 54 plasma data variables 52 units 55 urine data variables 53 Node licenses 21 P Parameter names 55 Partial AUCs 54 Pharsight common files 15 customer feedback 12 products 11 scientific and consulting services 11 technical support 11 training courses 11 PKS permissions required 19 versions supported 14 PKS Reporter versions supported 14 Processor 13 Product tracking ID 22 R RAM 13 Renewing floating licenses 27 S Sample Collection Points 46 SigmaPlot version 14 Study data Data Collection Points 48 dosing 46 Sample Collection Points 46 subject variables 46 Subject IDs 46 System settings 2 T Tau 54 Technical support 11 licensing 12 Training courses 11 U Units 55 User documentation 2 V Virus protection software 15 W Windows Index W version 13 WinNonlin required default options 18 version 14 99 WinNonlin AutoPilot User Guide 60
14. Pharsight WinNonlin AutoPilot Getting Started Guide Version 1 1 1 WinNonlin AutoPilot Version 1 1 1 WinNonlin AutoPilot Copyright 2007 Pharsight Corporation This software and documentation are owned by Pharsight Corporation and may be used only as authorized in the license agreement controlling such use No part of the software nor the accompanying documentation may be reproduced transmitted or translated in any form or by any means electronic mechanical manual optical or otherwise except as expressly provided by the license agreement or with the prior written permission of Pharsight Corporation This product may contain the following software that is provided to Pharsight Corporation under license Sen tinelLM 6 0 copyright 1998 Rainbow Technologies Inc All rights reserved Microsoft XML Parser ver sion 3 0 copyright 1998 2000 Microsoft Corporation All rights reserved GNU tree control copyright 2006 Free Software Foundation Information in the documentation is subject to change without notice and does not represent a commitment on the part of Pharsight Corporation The documentation contains information proprietary to Pharsight Corp and is for use by Pharsight Corporation customers only Use of the information contained in the documentation for any purpose other than that for which it is intended 19 not authorized Neither Pharsight Corp nor any of the contributors to this document makes any representat
15. Statistical Analysis Display Tables Graphs Appendix Se lables Selection Table Types Demographics Actual Times Actual Times Deviation Table Concentration Cumulative AUC Demographics Ed Lambda Z Actual Times PK Parameter A PK Parameter B Intet PK Parameter Actual Times Deviation iv Concentration Cumulative AUC Lambda Z PK Parameter A PK Parameter B Intext PK Parameter I gt Completion 20 Click the Appendix tab In the right pane in the Selected column select all but one appendix and click Remove to limit the number of appendices gener ated for this run 42 Testing the Installation Installation test PK Automation SETE Stratification Normalization Statistical Analysis Display Tables Graphs Data Location gt Study Specification gt Ouiput Specification Completion 21 Click Next after all of your selections have been made in this dialog The Automation Project has been configured dialog 1s displayed 43 4 44 WinNonlin AutoPilot Getting Started Guide The Automation Project has been configured The Automation Project will run with the following selections Windows User ID bcos Current System settings Version 1 1 0 0 2007 03 30_127 30 25 Path Default Settings Data Input Locations WinNon1in NWCA Model NCA AutoPilot Crossover Demo Carterolol Data Workbook AUTOPILOT CROSSOVER DEMO CARTEROLOL Pwo Study Data Path C Program Fi
16. able Automation study design Crossover Parallel Sort variables Subject X X X Treatment_Description X Period X Day X X X Lower times Relative_Actual_Time or X X X Relative_Nominal_Time Upper times Relative_Actual_End_Time or X X X Relative_Nominal_End_Time Volume Volume X X X Concentration Concentration variable X X X Carry alongs Sequence X Period X Treatment_Description X X a The variable Period is required as a Sort variable for a Cross over Replicated study design or as a Carry along variable for a Crossover Randomized study that includes inferential statis tics b The variable Day is needed as a sort variable only when the study has multiple full profile days c The variable Sequence is needed as a Carry along variable only for a Randomized Crossover that includes inferential statistics 99 WinNonlin AutoPilot 5 User Guide 54 Dosing regimen AutoPilot requires that dose data be specified in the WinNonlin model as is usual when running NCA models When using PKS study data WinNonlin draws all dose information e g val ues and units for single dose data from the PKS study data into the Dosing Regimen field of the NCA model That information carries over to AutoPilot For steady state conditions WinNonlin draws all dose information from the PKS study data with the exception of Tau dosing interval This value must be entered manually into the Dosing field for each profile in
17. called lservrc located in the directory containing your Pharsight software To expedite requests for license renewals upgrades or additions include the lseryre file in e mail to Pharsight at licenzetaipharzight com Back View Any Previously Installed License Keus Exit Enter your product tracking ID in the Product Tracking ID field Enter your contact information in the appropriate fields Type or paste your license key into the License Key Code field gt Pl e Y Click Install License Key A message box is displayed that confirms that your license information has been correctly installed License Code Manager E Your license code has been installed Please start your Pharsight product to confirm that your license code is working OK 7 Click View Any Previously Installed License Key s to display the Previ ously Installed License Code s message box 24 Licensing Install an AutoPilot 1 1 1 license 3 Note The Previously Installed License Code s message box contains the license code and other licensing information about your Pharsight software product Click Support to copy this information to the clipboard so 1t can be pasted into an e mail if you need to contact customer support 8 Click Exit to exit the message box 9 Click the Pharsight Licensing Wizard s Exit button when you are finished or click the lt lt Back button if you need to install another license The node license inf
18. can be activated Table 1 9 Formatted output text and appendix text Feature Configurable by administrator Configurable by user Selection Admin can determine which text items are From the list of available text items as deter available for the user and from this list ini mined by admin User can determine which tially create the default of available text items are actually generated per run i e User items can modify the Admin default for generated text output Formatting Admin can set the defaults for orientation User can modify all of the Admin formatting set paper size and margins and select the order and layout options for the graphs that are included in the text document that incorporates all the individual time concen tration excretion rate and percent dose remaining graphs tings on a per run basis About Pharsight Corporation 10 Pharsight Corporation provides software and services designed to improve the efficiency of drug development The company s proprietary technology and world class consulting expertise enable pharmaceutical and biotechnology companies to make more confident decisions in dealing with complex issues of drug development and product portfolio management Pharsight Corpora tion helps companies make more informed and objective decisions that lead to more successful and predictable trial outcomes Pharsight Corporation is a public company headquartered in Mountain View California M
19. ed Concentration variable Required Required Required Required Volume Required Required Required Required sequence Required Optional Optional Optional Demographics Categorical Optional Optional Optional Optional Demographics Continuous Optional Optional Optional Optional Midpoint_Time Optional Optional Optional Optional 50 Study Preparation NCA model requirements 9 Table 5 7 Variable requirements for urine data NCA models 210 212 Variable Study Design Optional Optional Optional Parallel Optional l Either XX RawCONC or XX PKCONC is required RCT Randomized Crossover Trial nRCT Non randomized Crossover Trial NCA model requirements AutoPilot PK Automation projects require an NCA model which is created in WinNonlin before running AutoPilot The model requirements vary depend ing on the study design selected in the AutoPilot User Module and the Win Nonlin NCA model used Model requirements fall into the following categories e Variables Sort X Y and Carry Along e Dosing Regimen e Regression Lambda z e Partial Areas e Model Options Variable assignments The tables below detail the WinNonlin NCA model requirements for plasma and urine matrices respectively for different PK Automation study designs The Sort Variables in the model must be ordered as they are presented in the table below e g Subject then Treatment Description Note Tro
20. ed the threshold are used for summary statis tics calculations Display of source Admin can set the default to display infor User can decide to apply the source data data mation in the form of a footnote regarding footnotes per tables and graphs indepen the source data study file in tables or dently per run and what parts of the source graphs information are displayed location path time and date Exclusion Admin can allow for exclusions and set If Admin enables exclusions User can how exclusions are displayed in final define the exclusion on a profile by profile tables and figures including correspond basis User can also define if corresponding ing footnotes graphs and tables created reflect the excluded profiles Display order Not applicable User can decide the order of the treatment identifiers e g treatment day etc that are displayed in in text tables top to bottom and x axis for categorical graphs left to right Introduction WinNonlin AutoPilot 1 Table 1 3 Business rules all output continued Feature Matrix mapping Configurable by administrator Admin can configure through addition or deletion matrix abbreviations and map to the concentration column headers to encompass full matrix names into the final tables and graphs For example PLS in the concentration column would equate to Plasma in the final output Configurable by user User cannot modify these sett
21. ense information sent contains the correct license code to be used Floating License The AutoPilot floating license is sent via e mail The license information sent contains the correct license code to be used 21 WinNonlin AutoPilot 3 Getting Started Guide For WinNonlin version 5 0 1 For WinNonlin version 5 0 1 the WinNonlin and AutoPilot licenses must be of the same type They both must be node or they both must be floating licenses The two licenses must be installed in the WinNonlin directory Installing a node or a floating license key code Use the Pharsight License Wizard to install both the WinNonlin and AutoPilot licenses For WinNonlin versions 5 1 1 and higher CAUTION WinNonlin 5 1 1 and higher and AutoPilot 1 1 have separate license wizards 1 The WinNonlin 5 1 1 and higher license wizard is located at All Pro grams gt Pharsight gt WinNonlin gt Pharsight License Wizard in the Win dows Start menu 2 The AutoPilot 1 1 1 license wizard 1s located at All Programs gt Phar sight gt WinNonlin AutoPilot 1 1 1 gt AutoPilot License Install Wizard in the Windows Start menu The license installation process will not work if a user tries to install licenses for both programs using the same wizard For WinNonlin versions 5 1 1 and higher WinNonlin and AutoPilot can have different license types For example WinNonlin can have a Node license and AutoPilot can have a Floating license The order in which you
22. er Orientation Time Scale Algorithm Exclusion Define Exclusion Criteria Output Options Limit of Quantification LOG AUC Extrapolation Threshold 8 Click Define Exclusion Criteria where you can add or remove profiles 34 Testing the Installation Installation test Excluded Profiles From Summary Statistics Sisi l Carterolo Treatment_Description Carterolol Rifampin Carterolol Carterolol Rifampin Carterolol Carterolol Rifampin Carterolol Carterolol Rifampin Carterolol Carterolol Rifampin Carterolol Carterolol Rifampin Carterolol Carterolol Rifampin Carterolol Carterolol Rifampin Carterolol Carterolol Rifampin Carterolol Carterolol Rifampin 2 E L 3 4 E 5 6 e L 8 E g 10 r e e Carterolol Carterolol Rifampin Carterolol Carterolol Rifampin dia l Unselect All Collapse All 9 In the left window select the appropriate checkboxes for the criteria you want to exclude from the summary statistics In the Sort Columns window on right you can move the selections up or down in the order preferred 10 Click OK after all of your selections have been made in this dialog 11 Click the Display Options tab 35 WinNonlin AutoPilot 4 Getting Started Guide PK Automation eS S G Z Stratification Normalization Statistical Analysis Display Tables Graphs Appendi
23. er can change the defaults that were set by Admin Summary statis Admin can determine which summary statis From the list of available summary statistics tics tics are available to be included in the table based on the Admin settings User can deter along with their order From the list of avail mine which of these summary statistics are able statistics Admin determines which sta actually included in the table and their order tistics are actually included and their default per run i e User can change the defaults ordering in the generated tables that were set by Admin Precision Admin can set the defaults for the precision of User can modify the Admin defaults for preci variables and summary statistic values sion per variable Precision choices include number of significant figures or decimal places WinNonlin AutoPilot Getting Started Guide Table 1 5 Formatted output tables Feature Configurable by administrator Configurable by user Formatting Tables are considered to be constructed from User cannot modify most of the formatting basic elements such as Header Body Foot options for tables The exceptions are the set notes Variable Names Variable Values etc tings for output setting which can be user Admin can set the font font style font size modified for a specific run alignment and underline no underline for these elements In addition the thickness of
24. help C Program Files Pharsight AutoPilot and sub directories Example input study data C Program Files Pharsight AutoPilot Examples PDF user manual C Program Files Pharsight AutoPilot User Docs Contact Pharsight Customer Support support pharsight com for a complete list of files that are installed with AutoPilot and their default locations The InstallShield Wizard is displayed when the installation is complete InstallShield Wizard InstallShield Wizard Complete Setup has finished installing Wini onlin AutoPilot on your computer Back Eancel Click Finish to exit the wizard AutoPilot requires a current license for WinNonlin See Licensing on page 21 for details and instructions Usage requirements The following settings are required before using AutoPilot 1 In WinNonlin click Tools gt Options and then set the following 18 Installation Installing AutoPilot 2 a Models Select Workbook Charts and Exclude profiles with insuffi cient data as Default Output Options b Units Select Show units with column headers Show units on chart labels and Show units on tables as Default Unit Options 2 Pharsight Knowledgebase Server if applicable a WinNonlin AutoPilot requires system level WRITE access to save results back to PKS or system level READ access to access data and save results to a local hard drive b If you are installing Autopilot and WinNonlin
25. ide System requirements For acceptable performance the following requirements are highly recom mended for a system running WinNonlin AutoPilot Table 2 1 System requirements for WinNonlin AutoPilot Item System software Minimum Windows 2000 Service Pack 4 Windows 2000 Japanese SP4 Windows XP Service Pack 2 Windows XP Japanese SP2 or Citrix Presentation Server 4 on Windows 2003 Recommended Windows XP Browser to view online help Microsoft Internet Explorer 5 0 or higher Internet Explorer 6 0 or higher Processor RAM Pentium II 1GHz 912 MB Pentium IV 1 4GHz 1GB WinNonlin AutoPilot 2 Getting Started Guide Table 2 1 System requirements for WinNonlin AutoPilot Item Minimum Recommended Hard disk space 60MB NA installation drive install footprint only excludes study data and generated output Graphics SVGA or better NA a Hard drive onto which AutoPilot is installed The following software must be installed on the system running AutoPilot Table 2 2 Required software Software Version s supported Version s recommended WinNonlin Profes version 5 0 1 5 1 1 or 5 2 version 5 2 sional or Enterprise SigmaPlot version 8 or later version 9 For Citrix version 9 or later Note A network license for Sigma Plot is required when running on Citrix Microsoft Word 2000 2003 20033 XP or XPJ XP or 2003
26. ilot for an Automation or Com parison run the available settings are governed by the system settings and the default settings System settings take priority over the default settings For many WinNonlin AutoPilot features the user can make selections for a spe cific run that override the administrator defined system settings allowing flexibility and control over specific analyses and output Conversely there are also several notable cases for which the configuration settings defined in the Administration Module cannot be modified in the User Module where for mats and business rules are considered to be part of SOPs See Administrator and user settings on page 3 for a description of features that are user or administrator configurable Documentation The WinNonlin AutoPilot User Guide covers AutoPilot installation adminis trator configuration and user settings and workflow for PK Automation and Comparison projects Those documents are available in Adobe Acrobat PDF format in the AutoPilot installation directory under User Docs Both user and administrator functions are included in the AutoPilot Online Help available from within the AutoPilot software via the Help or button Introduction WinNonlin AutoPilot 1 Administrator and user settings Some attributes in Autopilot are user configurable while others are only con figurable by the administrator The following tables list the configurable fea tures of WinNo
27. ings Concentration vari able used for concen tration final output Admin can set the default of which con centration column in the study data to use in the creation of the concentration tables and graphs independently User can select which concentration column in the study data to use in creation of the concentration tables and graphs indepen dently Table 1 4 Business rules tables Feature Table splitting Configurable by administrator Allows splitting of tables if they won t fit on one page per page type and in margins set in the Administration module Admin can enable or disable the table splitting feature for Users Configurable by user If Admin enables table splitting User can activate deactivate it per run Context sensitive footnotes display calculation of non numeric values for descriptive statistics Allows definition modification via addition or deletion of the default list of non numeric val ues e g NS and associated footnotes NS No Sample In addition Admin can config ure how these non numeric values are han dled during descriptive statistics calculations missing or zero User cannot modify these settings In text table tem plate Admin can configure the style including number of descriptive statistics and define if PK parameters are time dependent Also can default the specific descriptive statistics User can modify the selection of
28. ion or warranty nor shall any warranty be implied as to the completeness accuracy or usefulness of the information contained in this document nor do they assume any responsibility for liability or damage of any kind which may result from the use of such information Destination Control Statement All technical data contained in the software and documentation are subject to the export control laws of the United States of America Disclosure to nationals of other countries may violate such laws It is the reader s responsibility to determine the applicable regulations and to comply with them United States Government Rights The software and documentation constitute commercial computer software and commercial computer soft ware documentation as such terms are used in 48 CFR 12 212 Sept 1995 United States Government end users acquire the software under the following terms 1 for acquisition by or on behalf of civilian agencies consistent with the policy set forth in 48 CFR 12 212 Sept 1995 or 11 for acquisition by or on behalf of units of the Department of Defense consistent with the policies set forth in 48 CFR 227 7202 1 June 1995 and 227 7202 3 June 1995 The manufacturer is Pharsight Corporation 321 E Evelyn Avenue 3rd Floor Mountain View CA 94041 Trademarks AutoPilot PKS Pharsight Knowledgebase Server and Trial Simulator Pharsight WinNonlin WinNonMix Drug Model Explorer and DMX are trademarks or reg
29. ired Optional Required for repli cated else optional Day Required Required Required Required Required RAT Optional Optional Optional Optional Optional RNT Required Required Required Required Required XX_Dose Required Required Required Required Required 49 WinNonlin AutoPilot 5 User Guide Table 5 6 Variable requirements for plasma data NCA models 200 202 Variable Study Design RCT nRCT Replicated Parallel Trough All Concentration variable Required Required Required Required Required sequence Required Optional Optional Optional Optional Demogs Categorical Optional Optional Optional Optional Optional Demogs Continuous Optional Optional Optional Optional Optional l Either XX RawCONC or XX PKCONC is required RCT Randomized Crossover Trial nRCT Non randomized Crossover Trial Table 5 7 Variable requirements for urine data NCA models 210 212 Variable Study Design RCT nRCT Replicated Parallel Subject Required Required Required Required Treatment_Description Required Required Required Required Period Required Optional Required Optional Day Required Required Required Required RAT Optional Optional Optional Optional RNT Required Required Required Required RAET Optional Optional Optional Optional RNET Required Required Required Required XX_Dose Required Required Required Requir
30. istered trademarks of Pharsight Corporation S PLUS is a registered trademark of Insightful Corporation SAS and all other SAS Institute Inc product or service names are registered trademarks or trademarks of SAS Institute Inc in the USA and other countries Senti nelLM is a trademark of Rainbow Technologies Inc Microsoft the Internet Explorer logo MS DOS the Office logo PowerPoint Windows the Windows logo Windows NT the Windows Start logo and XL design the Microsoft Excel logo are registered trademarks of Microsoft Corporation Pentium and Pentium III are trademarks or registered trademarks of Intel Corporation Adobe Acrobat Acrobat Reader and the Adobe PDF logo are registered trademarks of Adobe Systems Incorporated All other brand or product names men tioned in this documentation are trademarks or registered trademarks of their respective companies or organi zations Pharsight Corporation 321 E Evelyn Ave 3rd Floor Mountain View California 94041 Voice 1 650 314 3800 Fax 1 650 314 3810 http www pharsight com support pharsight com Contents Chapter 1 Chapter 2 Chapter 3 Introduction er a 1 WinNonlin AutoPilot ooooooooooooooooo nooo ooooo l SYSE SEINES secrets E E Eko yn AOR ae ARAS 2 Documentation ii A A ee 2 Administrator and user settings oo 3 About Pharsight Corporation anasa ccc cee eens 10 GE oh Oho a ia eel ad dde 11 Scientific and consulting services 000 eee eee eens
31. les Pharsight AutoPi lot ExamplesAutoPi lot Crossover Demo Carterolol pmo Loaded Study From NcAMode l Data Output Location Save To Pap Yes PAP Path C Program Files PharsighttAutoPi10t APOUtT put DC 06 ADECONTigProject pap xml scenario Info WinNon1din NCA Model NCA Model 200 Extravascular Plasma Crossover Non Randomized Single Dose Time amp Concentration Variables Relative_Actual_Time conc PLS_Carterolol_PRCONC Units ng ml Treatment_Description Try to complete execution on error Run Automation 22 Click Run Automation to run a test automation AutoPilot runs the analysis in WinNonlin and generates tabular graphical and text output in the assigned output directory 23 After the run has completed successfully a confirmation message is dis played Navigate to the output directory which contains several Excel spreadsheets Word documents and plots 24 Exit AutoPilot Chapter 5 Study Preparation Data columns and NCA model setup Study data WinNonlin AutoPilot analyses require that study data include specific vari ables for automation input The variables fall into the following categories e Subject e Demographic e Dosing e Sample Collection Point SCP e Data Collection Point DCP Required and recommended variables are listed under Study data on page 45 Once the study data variables are defined the user must create a WinNonlin model that defines model settings a
32. ling AutoPilot InstallShield Wizard J Choose Destination Location x Select folder where Setup will install files Setup will install wint onlin AutoPilot in the following folder To install to this folder click Next To install to a different folder click Browse and select another folder Destination Folder CAProgram Files Pharsight4utoPilot Browse InstallShield Back Cancel Then click Next The following screen is displayed Start Copying Files x Review settings before copying files Setup has enough information to start copying the program files If you want to review or change any settings click Back If you are satished with the settings click Next to begin copying files Current Settings Username Steven Harris Company Name Pharmavizion Inc Installation Director C Program Files Pharsight 4uboPilot Be Installshield lt Back Cancel Click Next to begin the installation 11 You are asked whether to enable PKS access Choosing Yes allows the user to load input study data and save output using PKS in addition to a local non PKS folder Choosing No allows the user to only load input study data and save output to a local folder 12 The following content is loaded 17 WinNonlin AutoPilot 2 Getting Started Guide Note Note Table 2 3 AutoPilot installation content Description Default location AutoPilot software and online
33. lizations Not applicable User can select PK Parameters to be normalized by continuous demographics e g weight located in the study data The user can select up to two normaliza tion schemes per run WinNonlin AutoPilot 1 Getting Started Guide Table 1 2 Analysis settings continued Feature Configurable by administrator Configurable by user Stratifications Not applicable User can select output to be stratified summarized by discrete demographics e g gender located in the study data The user can select up to two stratification schemes and for each scheme they can define one or two stratification variables e g Gender Gender and Smoking per run Statistical analysis Not applicable During PK automation of crossover studies a user can select to run inferential statistics on PK Parame ters using WinNonlin s LinMIX BE tool Table 1 3 Business rules all output Feature Configurable by administrator Configurable by user AUC Extrapolation Admin can configure rule regarding the User can select whether to use the settings display of a flag or a replacement value if the rule is activated by Admin and can and associated footnote for PK parame also set the threshold value e g 30 ters selected by the Admin where the AUC extrapolation exceeds the threshold set by the user on an individual run The Admin can also specify which parameters are affected and if the values that exce
34. mail E mail support pharsight com fastest response time Web http www pharsight com support support_sflogin php Phone 1 919 852 4620 Fax 1 919 859 6871 Mail Pharsight Corporation 5625 Dillard Dr Suite 205 11 WinNonlin AutoPilot 1 Getting Started Guide Cary North Carolina 27518 For the most efficient service e mail a complete description of the problem including copies of input data model file pap file and or pcp file and instruc tions detailing how the error with AutoPilot originated as well as the ASCII output if applicable Licensing and product upgrades For license renewals and product upgrades contact Pharsight sales E mail sales pharsight com Telephone 1 888 708 7444 from US only Fax 1 650 314 3811 Request assistance with Pharsight software licensing by e mail or telephone E mail license pharsight com Telephone 1 919 852 4620 Customer feedback Submit requests for product enhancements and defect corrections by e mail fax or through Pharsight s customer support Web site E mail support pharsight com Web support pharsight com Fax 1 919 859 6871 12 Installation System requirements and installation instructions Chapter 2 Review the following material before installing WinNonlin AutoPilot e System requirements below e Installing AutoPilot on page 14 Note For installation instructions for WinNonlin see the WinNonlin Getting Started Gu
35. med Individual values of zero treated as missing Admin can configure a rule that allows val ues of 0 to be treated as Missing prior to any summary statistic calculation User cannot modify these settings LOQ replacement and display Admin can configure a rule that allows replacement of numerical values with text values and corresponding footnotes if value is less than the threshold set by the user per run value of 0 01 is replaced with BQL Also can configure which PK parameters are governed by this rule User can decide whether to use the rule and set the replacement threshold that is used Time deviations cal culation flags and footnotes Allows Admin to select how the time devia tion is calculated and how time deviation is displayed threshold footnote and footnote flag User cannot modify these settings Display of missing references Admin can configure the display including value and corresponding footnote for miss ing values for the following table types time concentration demographics all others User cannot modify these settings Relative nominal time replacement Admin can apply the rule and configure the associated footnote that if relative nominal times are used instead of relative actual times each concentration value is flagged in the time concentration tables and has an associated footnote assigned User cannot modify these settings
36. nd parameters for an AutoPilot automation project Specific model requirements are given under NCA model require ments on page 51 Variable names Variable names are not fixed AutoPilot administrators can map study data variable names used in your organization to AutoPilot system variables and also assign custom output column names display names for the final tables graphs and so on as needed In addition the WinNonlin configuration file DEFAULTNCAPARAMETERNAMES MAP can be used to map WinNonlin 45 WinNonlin AutoPilot 5 User Guide custom PK parameter names to AutoPilot See the WinNonlin user documen tation for instructions Data variables The tables below list the default variables for an AutoPilot ready study including required variables and additional variables that are often useful AutoPilot administrators can add variables by providing the name category and data restrictions such as discrete or continuous Associated units from these added variables are taken directly from the column headers in the study data In the tables below WinNonlin name refers to the required column name as the data is displayed in WinNonlin Display name is the default column name used in final AutoPilot output An administrator can specify custom WinNonlin and display names See Required data variables by study type on page 49 for a listing of required and optional variables for each study type See NCA m
37. nlin AutoPilot and describes the modifications that administrators and users can make Table 1 1 Input settings Feature Administrator User Study data column nomenclature Admin can configure the mapping of User cannot modify these set configuration column mapping study input column headers to system tings names in AutoPilot and has ability to create new demographic variables e g phenotype and define the data type e g discrete Also can define the concentration column header potentially for matrix and analyte per the concentration variable template Selection of study data and output Not applicable other than upon instal User can select the input load location to use in an Automation or lation the ability to decide if PKS can study and output save AutoPi Comparison run be used as an input and output loca lot objects created to PKS and tion or non PKS local destinations through a standard browsing feature Saving a project from an Automation Not applicable User can name browse to loca or Comparison run tion and save a pharsight auto mation project pap or pharsight comparison project pcp that encompasses all user interface selections made in that run Table 1 2 Analysis settings Feature Configurable by administrator Configurable by user Selection of study Not applicable User can select study design type and subtype e g design Crossover Randomized Norma
38. odel requirements on page 51 for a listing of required variables by NCA model Table 5 1 Subject variables WinNonlin Display Default Default Default Comments name name units precision restrictions Subject Subject NA No Alphanumeric string Patient subject identifier Table 5 2 Dosing variables WinNonlin name Dose Display name Default Default Default Comments units precision restrictions Dose Yes dec 0 Numeric Dose administered Table 5 3 Sample Collection Points SCPs WinNonlin name Relative Nominal _Time Display name Default Default Default Comments units precision restrictions Nominal Time Yes dec 2 Numeric Protocol nominal time of sampling since last dose Used for Time Time Conc and Cumul AUC output and possibly X var in model 46 Study Preparation Study data 9 Table 5 3 Sample Collection Points SCPs continued WinNonlin name Display name Default Default Default Comments units precision restrictions Relative_Actual_ Actual Time Yes dec 2 Numeric Actual time of sampling since last Time dose Used for Time Time Conc out put Often used for the X var in model Relative Nominal Nominal End Yes dec 2 Numeric Two purposes Observation sheet _End_Time Time actual interval end time from last dose of sampling for urine Upper Time in model and Do
39. on open the Pharsight Licensing Wizard Enter the contact information if desired This information is saved in the license key file which you can use to provide Pharsight with information for license renewals and customer support correspondence Enter the license key code included with your product shipment or license renewal e mail Click Install License Key to save the information to the license key file and install the license and then click OK Click Exit to close the wizard To install a floating license for AutoPilot 1 1 1 1 From the Windows Start menu go to All Programs gt Pharsight gt WinNonlin AutoPilot 1 1 1 gt AutoPilot License Install Wizard The Pharsight Licensing Wizard is displayed 2 Click Floating License to install a floating license for your local copy of 26 AutoPilot 1 1 1 Figure 3 2 Install floating license wizard El Pharsight Licensing Wizard Enable Floating License Server This step should be done by a system administrator The Pharsight Floating Network License Server must be installed and set up on the server machine before this step iz attempted See the Getting Started Guide for detailed instructions 1 Enter the name of the server on which the floating 27 0 01 license server has been installed R S TR AE Ue gee Lie Enable Client PC to use License Server lt lt Back Exit Licensing Renewing a floating license key code 3 3 Enter the IP add
40. onlin in the same manner when a user performs an automation run After the automation run is 2 WinNonlin AutoPilot 3 Getting Started Guide complete AutoPilot releases the licenses back into the pool of available float ing licenses The problem If a company has two AutoPilot floating licenses and two WinNonlin floating licenses and there are three users who all need to use AutoPilot all three users could successfully load AutoPilot without receiving a licensing error message However once the third person starts her automation run then she will receive an error message from AutoPilot Failed to obtain license informa tion The solution Purchase enough licenses to satisfy user needs or ensure that users are aware that the number of simultaneous automation runs is limited by the number of available valid licenses 28 Chapter 4 Testing the Installation Confirming proper installation of WinNonlin AutoPilot To test that the AutoPilot installation has been successful you can generate limited output tables graphs and appendices using sample data files pro vided with the software If you select all default tables graphs and appendi ces the automation run 1s time consuming because of the volume of the output However by following these instructions a time consuming run is avoided CAUTION This chapter is not a full validation of the AutoPilot software Installation test To confirm tha
41. ore information is available on the Web at www pharsight com Introduction About Pharsight Corporation 1 Products Pharsight offers a comprehensive suite of software products including Win Nonlin WinNonMix Pharsight Trial Simulator Drug Model Explorer and the Pharsight Knowledgebase Server suite of products For further information please visit Pharsight on the Web at www pharsight com Scientific and consulting services Our scientific consultants can design and optimize clinical trials and clinical development programs to meet an individual company s objectives Pharsight Scientific Services are project centered planned and delivered in accordance with specific needs and agreed upon objectives Consultants can facilitate e Gathering and interpreting data e Building drug and population models e Guiding variability testing and trial optimization e Addressing specific development program objectives e Process automation Training Pharsight Corporation offers workshops and training courses at regular inter vals On site training 19 available by request Contact Pharsight for schedules pricing and availability The training schedule is also available on Pharsight s corporate Web site at www pharsight com training Technical support Consult the product documentation to address questions If further assistance is needed contact Pharsight technical support by e mail or Web preferred phone fax or
42. ormation is written to the LSERVRC file which is located by default at C Program Files Pharsight AutoPilot 10 Load AutoPilot 1 1 1 to ensure that the product tracking ID and license key information entries were successful To install the floating license server 1 Load the AutoPilot CD into the computer that will act at as the Floating Net work License server 2 Run the LicenseServerlnstall exe file which is located in the AutoPilot CD s Floating License Server directory The default directory path to the executable is D Floating License ServenlLicenseServerlnstall exe 3 Follow the instructions in the installation wizard CAUTION The Pharsight Floating License Server must be installed in the process space of the intended server It must be installed and run on the server itself and not on a mapped drive on a client machine To install a floating license on the license server 1 Open the Windows Start menu on the network server and choose Pro grams gt Pharsight gt Pharsight Floating License Server gt Pharsight License Wizard for Server The Pharsight License Wizard for Server window 1s displayed 25 WinNonlin AutoPilot 3 Getting Started Guide 2 Enter the Product Tracking ID which was included with your AutoPilot ship Note ment or license renewal e mail Refer to this number in all correspondence with Pharsight about this product license To locate the Product Tracking number after installati
43. phs from this list initially create the default list of available determined by Admin User can graphs determine which of these graphs are actually generated per run i e User can modify Admin default for gener ated graphs Output details Admin can determine default values for output details User can modify all of the output on the graphs that are generated Depending on details on a per run basis graph type these details can include e Creation of lin and or log y axis e Display of a summary value such as mean or median Display of an error value such as Standard Devia tion or Standard Error e Display of up and or down error bars Display of regression line for PK Parameters Display of LOQ lines for PK Parameters WinNonlin AutoPilot 1 Getting Started Guide Table 1 8 Formatted output graphs Feature Configurable by administrator Configurable by user Formatting Admin can determine the following formatting options User cannot modify most of the for graphs options for the formatting of graphs e Print options such as orientation paper size and An exception is the print orientation margins portrait vs landscape e Text elements of a graph such as title legend and labels can be activated or deactivated and the for mat font font style font size line thickness can be set Line elements of a graph such as grid lines error bars axis line tick lines etc
44. ress of the server on which the Pharsight Floating Network License Server 1s installed For example 127 0 0 1 Note 127 0 0 1 is a generic server IP address that is used as an example for this set of instructions Your actual server IP address will be different 4 Click Enable Client PC to use License Server A message box is displayed License Code Manager Server 127 0 0 1 has been defined OK 5 Click OK to continue 6 Click the Pharsight Licensing Wizard s Exit button when you are finished or click the lt lt Back button if you need to install another license The floating licensing information is written to the LSHOST file which is located by default at C Program Files Pharsight AutoPilot 7 Load AutoPilot 1 1 1 to ensure that the product tracking ID and license key information entries retrieved were successful Renewing a floating license key code To renew a floating license enter the new license key code and product track ing ID on the network license server using the Pharsight Floating License Wizard for Server No changes are necessary on the client systems AutoPilot floating license issue When AutoPilot is launched it searches for a valid license for both AutoPilot and WinNonlin If both licenses are found then AutoPilot opens and it releases the AutoPilot and WinNonlin licenses back into the pool of available floating licenses AutoPilot retrieves floating licenses for AutoPilot and WinN
45. separation lines e g between the header and body of a table can be set and grid lines can be switched on and off Output settings such as paper size US Letter vs A4 and ori entation portrait vs landscape can be con figured and set as defaults per table type Table 1 6 Business rules graphs Feature Administrator User Time Scale factors set on a per time scale Admin can configure time scale factors indepen dently for each time scale range to define the num ber of major ticks based on minutes hours days User can make changes for individ ual runs range basis and weeks for time concentration graphs Admin can also configure if all concentration graphs have the same scaling and ticks independently for the x and y axis Display analyte Admin can default to have independently the Matrix User can independently have the matrix and day e g Plasma Analyte e g Parent and Day e g Day 1 be displayed in the final graph as labels Matrix e g Plasma Analyte 6 0 Parent and Day e g Day 1 be dis played in the final graph as labels X Axis format for categorical graphs Admin can default if categorical graphs have split or offset display for the x axis User can select if categorical graphs in a run have split or offset display for the x axis Axis starting points Admin can default independently to either force the X axis and or y axis to start from zero or not
46. sight Automation Project files respectively and are applied to additional study data AutoPilot File Explorer is a WinNonlin AutoPilot utility that helps users pre pare reports that use AutoPilot graph and table output AutoPilot File Explorer loads the WMF graphs and XLS tables from WinNonlin AutoPilot project output files and exports them into Microsoft Word documents and PowerPoint 1 WinNonlin AutoPilot 1 Getting Started Guide presentations You can access AutoPilot File Explorer from the Microsoft Windows Start menu or by launching AutoPilot and clicking Explorer System settings WinNonlin AutoPilot comes pre configured and ready to use out of the box with default settings Designated WinNonlin AutoPilot administrators authenticated by user name and password can modify these settings and adjust them to meet a company s or working group s SOPs The Administra tor defined settings or system settings define the default options available to users for automation and comparison projects The settings are stored in an XML file that can easily be transferred from one computer to another or made part of an internal distribution for consistent implementation across an organi zation The file content is altered using the Administrator interface This file can be selected using the System Settings dialog box which is accessed by clicking System Settings on the main AutoPilot screen When a non Administrator user starts AutoP
47. sing sheet nominal end time for infusion Relative_Actual_ Actual End Yes dec 2 Numeric Two purposes Observation sheet End_Time Time actual interval end time from last does of sampling for urine Upper Time in model and Dosing sheet actual end time for infusion Matrix _ Ana Matrix Ana Yes sig 3 Numeric or Concentration of sample collected ytelD _ Route _ lytelD Con identified as Every column name that uses this centration Missing template is identified as a concentra tion column for example Matrix _ AnalytelD _RawCONC Volume Volume Yes dec 0 Numeric Sample Collection Volume Required for Urine Models 210 212 only Midpoint Midpoint_Time Yes dec 2 Numeric Midpoint_Time is the calculated time point that is equidistant between the Lower and Upper collection times of a given urine collection interval Rate Rate Yes sig 3 Numeric Rate is the excretion rate for each interval amount eliminated per unit of time Concentration Volume Ending time Starting time a Matrix is replaced with the matrix value from the study data AnalyteID is replaced with the Analyte ID from the study data Using the Administrator module an administrator can configure the concentration columns regarding name use and order of Matrix and Ana lyteID 47 WinNonlin AutoPilot 5 User Guide Table 5 4 Data Collection Points WinNonlin Display Default Default Default
48. splayed in Auto Pilot directly from the WinNonlin model pmo output unless specified dif ferently in this document Parameter names AutoPilot accepts either one of the following conditions e WNL Default PK Parameter names e A DEFAULTNCAPARAMETERNAMES MAP file as described in the Win Nonlin User s Guide e Do not exclude any parameters from the model output All other options should be left at their default values AutoPilot settings con trol those elements of the analysis and output CAUTION Any changes to parameters names in the Model Options dialog could cause erroneous results 55 WinNonlin AutoPilot 5 User Guide 56 Index A Anti virus software 15 Automation NCA model requirements 51 AutoPilot 1 admin and user settings 3 documentation 2 installing 14 C Common files 15 Customer support 11 licensing 12 user feedback 12 D Data Collection Points 48 Data variables 46 required by model 51 required by study type 49 Defect reports 12 Dosing study data 46 Dosing regimen 54 Tau 54 E Enhancement requests 12 F Floating licenses 21 renewing 27 l Installing AutoPilot 14 Internet Explorer 13 K Key codes See License key codes L Lambda Z 54 License key codes 22 floating 21 node 21 renew floating 27 Licensing customer support 12 57 WinNonlin AutoPilot User Guide 58 M Microsoft NET 14 Microsoft Excel version 14
49. start automatically From the Windows Start menu choose Run b Inthe Run dialog box type d setup where d is the letter assigned to the CD ROM drive and click OK 9 The software scans the system for a previous installation of AutoPilot If one is located remove it then re launch the installer step 4 above to proceed 6 The following Welcome screen is displayed 2 16 WinNonlin AutoPilot Getting Started Guide InstallShield Wizard o x Welcome to the InstallShield Wizard for WinNonlin AutoPilot The InstallShield Wizard will install Wind onlin AutoPilot on pour computer To continue click Next Back Cancel Click Next The user license agreement is displayed Click I Agree 8 The customer infomation screen is displayed Type the primary user s name and company optional InstallShield Wizard Customer Information Please enter your information User Name Steven Harris Company Name Pharmvision Inc Install this application for IY Anyone who uses this computer all users Only for me InstallShield Back Next gt Cancel 9 Select whether you want the software to be available to all users who log onto the computer or only the currently logged in user Then click Next 10 Click Browse to locate the folder into which to install Autopilot The default installation location is C PROGRAM FILES PHARSIGHT AUTOPILOT Installation Instal
50. summary Statistics Mean SD etc but cannot mod ify the style nor PK parameters assigned to time dependent Display of different sample sizes in in text tables Admin can configure a rule that will display if there are differences in sample size used to calculate summary statistics for PK parame ters via flags and corresponding footnotes User cannot modify these settings WinNonlin AutoPilot Getting Started Guide Table 1 4 Business rules tables continued Feature Calculation display of summary statis tics for small sample sizes Configurable by administrator Admin can configure rule that allows the val ues of summary statistics involved with small sample sizes 1 3 to be overwritten by text values and apply corresponding footnotes e g NC Not calculated sample size is too small Configurable by user User cannot modify these settings Significance level is displayed in statis Admin can configure a threshold for the dis play of p values e g 0 05 along with a cor User cannot modify these settings tics tables responding footnote to be displayed or replaced by non numeric text if the value is lower than the threshold Summary statistics Admin can configure a rule to seta minimum User cannot modify these settings based on thresh old percentage of values relative to total sample size that must exist in a profile before calcu lations are perfor
51. t AutoPilot is successfully installed and working with WinNonlin 1 Double click the AutoPilot icon on your Windows desktop The AutoPilot main window is displayed 29 WinNonlin AutoPilot 4 Getting Started Guide a la toe Its PK Automation Automation TT System Settings gear a a PE PK Compson Administrator Explorer WinNonlin AutoPilot Administra tor gt Comparison WinNonlin Formatted PK Output 2 Click PK Automation The PK Automation window is displayed 3 Click Local Study Data then click Load Study or Project File 30 Testing the Installation Installation test PK Automation Information WinNonlin NCA Model oo Model Workbook yq o er Study Data Path e ooo o o Project File PAP Path E Output Location Project Filename pap AOBConfigProject C Program Files Pharsight Auto Pilot APO Ltput bcoe 4 In the AutoPilot installation directory locate the EXAMPLES folder and open the example file AUTOPILOT CROSSOVER DEMO CARTEROLOL PMO AutoPilot launches WinNonlin to locate the model and associated data files and load the appropriate settings into the PK Automation wizard This step confirms successful communication between AutoPilot and WinNonlin 9 If desired edit the local directory under Output Location to specify a directory to contain test output Then click Next to proceed to the Study Specification page 31 WinNonlin AutoPilot 4 Getting Star
52. ted Guide PK Automation _ PK Auto BEEJ iSS 7 i Crossover T Parallel Non Randomized Time Relative _Actual_ Time Concentration PLS_Carterolol_PKCONC Wat Relative_Nominal_Time Lambda z Regression Enabled Partial Areas Detected 1 Calculation Method Linear Log Trapezoidal Data Location gt Sfudy Specification gt Output Specification gt Completion IY of p p p 6 For this example the default options are correct This step confirms that AutoPilot is reading the NCA model pmo file with the correct attributes Click Next The Output Specification page is displayed 32 Testing the Installation Installation test 4 PK Automation SIS Sue Z Stratfication Normalization Statistical Analysis Display Tables Graphs Appendix Stratification Stratification A Statistical Analysis FT Calculate PK Parameter Ratios Calculate Inferential Statistics eg Bioequivalence Data Location gt Study Specification gt Output Specification gt Completion Note the other 4 tabs These tabs are explained and displayed as you progress through this wizard Click the Display tab to set the parameters Note the Output Options tab on this page is selected by default 33 WinNonlin AutoPilot 4 Getting Started Guide PK Automation SISI Stratification Normalization Statistical Analysis Display Tables Graphs Appendix Output Options Display Options Display Ord
53. ugh analyses do not require an NCA model 91 WinNonlin AutoPilot 5 User Guide Table 5 8 NCA requirements for plasma data models 200 202 Variable Automation study design Crossover Parallel Sort variables Subject X X X X Treatment_Description X Period X Day X X X X X variable Relative_Actual_Time or X X X X Relative_Nominal_Time Y variable Concentration variable X X X X Carry alongs Sequence X Period X Treatment_Description X Relative Nominal Time X X X a The variable Period is required as a Sort variable for a Cross over Replicated study design or as a Carry along variable for a Crossover Randomized study that includes inferential statis tics b The variable Day is needed as a sort variable only when the study has multiple full profile days c The variable Sequence is needed as a Carry along variable only for a Randomized Crossover that includes inferential statistics d If the variable Relative Nominal Time is not used as the X variable in the NCA model 1t must be assigned as a Carry along in order to create the Cumulative AUC output table 92 Study Preparation NCA model requirements 9 Table 5 9 NCA requirements for urine data models 210 212 Vari
54. x Output Options Display Options Display Order Orientation Time Scale Algorithm S CS Decimal Alignment Automatic Splitting X Axis Display Matrix Y Display Analyte v Y Concentration Output Variable Used PLS Carterolol PKCONC w PLS Carterolol PKCONC wv M Include Source Information Tables Graphs Texts Y Source Location V Include path Y Source Location V Include path Y Source Location V Include path Ie Date and time stamp Ie Date and time stamp Ie Date and time stamp Data Location gt Study Specification gt Output Specification Completion 12 Click the Display Order tab Use this page to rearrange the Treatment Description options 36 Testing the Installation Installation test PK Automation Siratification Nomalization Statistical Analysis Display Tables Graphs Appendix Output Options Display Options Display Order Orientation Time Scale Algorithm Treatment Description Carterolol Carterolol Rifampin EEE TTC Sc Tee Se TSS eT SST Te SS ee ee ee bcoe Data Location gt Study Specification gt Output Specification gt Completion AE 13 Click the Orientation tab Use this page to select the portrait or landscape options in the Tables Time Concentration Graphs PK Parameter Graphs and Appendix items 3 WinNonlin AutoPilot 4 Getting Started Guide PK Automation EJ S SSU D Z Stratification Normalization Statistical Anal
55. ysis Display Tables Graphs Appendix Output Options Display Options Display Order Orientation Time Scale Algorthm Orientation fem 2 L L A vergas Tables Time Concentration Fortrait PE Parameter Fortrait Intext Portrait Individual Subject Portrait Individual Subject by Treatment Fortrait Summary E Portrait Categorical Standard Fortrait Categorical Box and Whisker Fortrait Continuous Dose E Portrait Individual Time Concentration Letter e All linear then all log Summary PK Text E 38 Testing the Installation Installation test 14 Click the Graphs tab PK Automation Seles Stratification Normalization Statistical Analysis Display Tables Graphs Appendix Time Concentration Categorical PK Parameter Graphs El PK Parameter A 3 aus Categorical Standard alo Al A Categorical Box 4 Whisker Continuous Dose Standard Continuous Dose Box 4 Whisker Continuous Demographic W Continuous Dose Standard W Continuous Dose Box amp Whisker PK Parameter vs Continuous Dose Graphs PK Parameter vs Continuous Demographic Graphs W Continuous Demographic Demographic 1 lAge Demographic 2 15 For this test run deselect all check boxes except Categorical Standard 16 In the left window select Categorical Standard in the PK Parameter cate gory Select the appropriate checkboxes in the tables that will display An example of the Categorical Standard table is displayed
Download Pdf Manuals
Related Search